Biofilms are mucilaginous communities of microorganisms such as bacteria, archaea, fungi, molds, algae or protozoa or mixtures thereof that grow on various surfaces. Biofilms form when microorganisms establish themselves on a surface and activate genes involved in producing a matrix that includes polysaccharides. This matrix may provide protection of biofilm forming bacteria from biocides.
Under certain circumstances, however, biofilms can be undesirable. For example, biofilms can cause damage to equipment such as cooling systems, or aquaculture equipment by corrosion of the equipment by microorganisms residing in the biofilm or by excessive coating or film buildup compromising the normal mechanics of the equipment. Biofilms can also have very detrimental health effects. For example, many hospital-acquired infections involve biofilms, which can contaminate implants and catheters and prevent adequate antimicrobial treatment of such devices. Biofilms also result in adverse health conditions ranging from lung infections as in cystic fibrosis to more prevalent diseases such as tooth decay.
Regarding oral biofilms, certain bacteria can produce highly branched polysaccharides, which together with other microorganisms from the oral cavity form adhesive matrix films facilitating the proliferation of plaque. Left untreated, these oral biofilms can eventually lead to dental caries, gingival inflammation, periodontal disease, and tooth loss. As oral biofilm continues to accumulate, rock-hard white or yellowish deposits can arise. These deposits are called calcified plaque, calculus or tartar, and are formed in the saliva from plaque and minerals, in particular calcium. Established oral biofilm can be very difficult to disrupt whether by mechanical or chemical means. This can be particularly problematic in domains where mechanical removal is not feasible (depending on the implement).
Mechanical removal is an effective methodology used to disperse biofilms. In the case of oral biofilms, toothbrushes, floss, picks, etc. have been used. One limitation of mechanical removal is the ability of the mechanical action to reach the biofilm coated surfaces. This is particularly difficult between teeth and at the tooth/gum line interface.
Another method for preventing or disrupting a biofilm is to interfere with the quorum-sensing signals. Quorum-sensing signals are molecules that help trigger and coordinate part of the process of forming a biofilm. Bacteria constantly secrete low levels of the signals and sense them either through receptors on their surfaces, or internally. The receptors trigger behavioral changes when there are enough bacteria to allow the signals' concentrations to achieve a critical threshold. Once this occurs, bacteria respond by adopting communal behavior, such as forming a biofilm, and in the case of pathogenic bacteria, deploying virulence factors such as toxins. In addition to communicating with members of their own species, bacteria also conduct interspecies communications, such that a biofilm may involve and/or contain more than one species of bacteria. Chemicals have been developed that bind but fail to activate the receptors of quorum-sensing signals or that interfere with signal synthesis. Enzymes that degrade the signals have also been developed.
Strong antimicrobials may be used to kill bacteria in a biofilm, controlling its development and growth. However, once biofilms are established, antimicrobials are not associated with removal of live or dead biofilm. It has been well documented that, because antimicrobials have difficulty penetrating the biofilm's surface layer, they are less effective on bacteria in an established biofilm compared to planktonic bacteria. Agents that help antimicrobials penetrate the biofilm's surface layer improve the effectiveness of the antimicrobials.
Recently, several biofilm dispersing agents have been identified that can be used to signal select bacteria to release from an established biofilm. Signaling agents could help to disperse bacteria, however, signaling compounds have not been shown to be effective on all oral bacterial species, and often need optimized conditions and long contact times to show functionality.
There is, therefore, an ongoing need to identify agents that function as compounds, compositions, and methods for disrupting biofilms. In certain embodiments, the present invention provides certain unsaturated long chain alcohols and/or aldehydes which disrupt biofilms and disperse single and mixed species bacteria from the biofilm.